T Bouillon MD, D Kietzmann MD*, I Meineke PhD**, R Port MD§, A Hoeft MD
Dept of Anesthesiology, University of Bonn, 53105 Bonn; *Dept of Anesthesiology and **Dept of Clinical Pharmacology, University of Göttingen, 37075 Göttingen, §German Canter Research Institute, 69120 Heidelberg
Introduction: Piritramide, a synthetic opioid, is currently investigational drug in the United States. This study was designed to characterize the pharmacokinetics (PK) of the drug in ASA I-II patients including covariate analysis.
Methods: After having obtained institutional approval and informed consent, 29 ASA I-II patients undergoing minor elective ENT or ophthalmologic surgery (14 males, 15 females; age: 21-82y; weight: 49-93kg) were included into the study. They received 0.2mg/kg of piritramide as an intravenous bolus prior to induction of anesthesia with etomidate, pancuronium, and succinylcholine. After endotracheal intubation, anesthesia was maintained with O2/N2O (1:2) and isoflurane as indicated clinically. Blood samples were drawn for up to 48 hours after administration of the drug. The plasma levels of piritramide were determined with a validated HPLC method. The data were analyzed by mixed effects modeling, using NONMEM version IV. A three compartment mamillary model, parameterized in terms of clearances and distribution volumes was fitted to the data. Covariates tested were sex, age and weight. The log-likelihood criterion was used for covariate inclusion/deletion (p<0.01).
Results: The PK parameters of piritramide are displayed in the table. The population means refer to an age of 47y and a body weight of 74kg (medians of the study population).
| Parameter Volumes (l) | Mean (SE) | Interind. Variability |
| Central | 51 (5.3) | 31-83 |
| Peripheral 1 | 150 (11.8) | 111-203 |
| Peripheral | 2 212 (15.6) | 156-288 |
| Clearances (l/h) | ||
| Central | 34 (1.6) | 27-42 |
| Intercompartm. | 1 495 (50.7) | 343-715 |
| Intercompartm. | 2 48 (8.4) | 34-68 |
Distributional and elimination half lives are 0.05, 1.34 and 10.43h and îpercent coefficients”1 79, 13 and 8. Elimination clearance decreases 6% per decade, the peripheral volumes of distribution increase 9% and 6% per decade between 20-80 years. The fast intercompartmental clearance increased 20% per 10kg of body weight between 50 and 90kg.
Conclusions: Piritramide undergoes extensive and fast distribution and slow elimination, quite similar to sufentanil2. As with this drug, the decrease of plasma concentrations after short time administration is almost entirely due to distribution.
1 Anesthesiology 76: 327-330, 1992
2 Anesthesiology 83: 1194-1204, 1995
Reference: PAGE 5 () Abstr 577 [www.page-meeting.org/?abstract=577]
Poster: poster